The Morphology-Neuropathology portion of this Core will be the histology facility for all the projects and will provide the expertise required to perform the detailed morphologic studies that have been proposed for the animal models of Rett Syndrome, and for comparative studies on Rett and non-Rett brain. The Core will work intimately with each of the projects as follows: For projects 1 and 2: To support studies on the relation between genotype and phenotype in Rett syndrome, the core has autopsy material on a number of patients suitable for clinical, morphologic-molecular correlation studies. For project 1: The core will perform the morphologic characterization of the proposed animal model for Rett syndrome, comparing it to wild-type animals and to defined alterations seen in Rett. For project 3: The core will test and titrate the MeCP2 antibodies for use with human and animal tissues and will use them for detailed investigation of the cellular expression of the MeCP2 protein in the developing and adult human and mouse brain, and in Rett syndrome. The investigation of brain specific candidate proteins (e.g. trophic factors) defined by cDNA micro array analysis to be disrupted in cells expressing mutant MeCP2 will be studied in Rett tissues using immunohistochemical methods. The differentiation of cell types in the established embryoid bodies will be characterized by the Core using antibodies to neuro-epithelial precursor cells and the effects of the introduction of mutated MeCP2 into this system will be characterized morphologically The morphologic effects of folic acid treatment on the normal mouse and on the MeCP2 deficient mouse will be determined with gross and microscopic examination of body and brain tissues. The core director, Dawna Armstrong and her associate, Barbara Antalffy, have successfully provided a similar core facility for the Mental Retardation Research Center at Baylor College of Medicine. Moreover, they have been directly involved with the neuropathological study of Rett syndrome wince 1986 and have a well established autopsy and neuropathology data base for Rett syndrome. The Morphology- Neuropathology Core laboratory is located near the main Baylor laboratories where completely equipped to perform routine histology with frozen, fixed or cultured tissues, classic neuropathologic studies of neurons, myelin, axons, dendrites and spines, histochemistry and immunocytochemistry. The Administrative and Data Analysis Core portion of this Core is small but essential to the smooth operation of the Program Project. Huda Zoghbi will be responsible for the overall administration of the Project. She will work closely with the other principal investigators who compose the Executive Committee Regular meetings of the Executive Committee with the Internal Advisory Board will gauge progress, aid in scientific problems, and assist during major administrative decisions. The External Advisor will visit the site once a year for 2 days. Research will be presented, and a formal meeting of the Executive Committee and the External Board on the second day will review the progress of the work and provide thoughtful suggestions on how to improve or hasten that progress. Dr. Zoghbi will be assisted in the administrative and financial management of the Project by Gay Horelica, Administrative Assistant. Gay will coordinate daily administrative and financial affairs of the researchers and will ensure seamless communication and interaction among the researchers. Dr. Alan Percy will travel to Baylor twice a year for this project, and Gay will see to his travel needs. Dr. O'Brian Smith will assist the various investigators (Glaze, Zoghbi, Van den Veyver, Percy, and Armstrong) with analysis of data from phenotype/genotype correlation studies (Projects 1, 2), microarray gene expression studies (Projects 1, 3) quantitative neuropathological studies provided in the various projects under the relevant specific aims.